The acidic sulfonimidation of aryl–oxazolines and the electrophilic fluorination of aryl–oxazolines

Abstract

Aryl oxazolines have been employed as directing groups for several different coupling reactions. In the exploration of using phenyl oxazoline as a directing group for electrophilic fluorination, it was discovered that acidic sulfonimide nucleophiles including dibenzenesulfonimide, o–benzenesulfonimide, dimethanesulfonimide, and N–(methylsulfonyl)–benzenesulfonamide are discovered to open a variety of alkyl, aryl and heteroaryl–2–oxazoline rings to provide the sulfonimidation products in refluxing 1,4–dioxane. The electron rich 2–oxazoline substrates worked well for the nucleophilic ring opening reactions while no reaction took place for the electron poor 2–oxazoline substrates. 4,4–dimethyl–2–phenyl–2–oxazoline was thus rationally designed inhibit sulfonimidation and to act as a removable ortho directing group for the palladium catalyzed C–H electrophilic fluorination of arenes. Using NFSI as the fluorinating agent, and a Pd(II), Ag(I) catalytic system, electrophilic C(sp2–H) ortho–fluorination took place on a variety of aryl substrates to afford the corresponding mono and di–fluorinated products. The oxazoline directing group was then hydrolyzed unmasking the carboxylic acid moiety, demonstrating the synthetic utility of this reaction